PB2381: EFFICACY ANALYSIS OF BRUTON’S TYROSINE KINASE INHIBITOR COMBINED REGIMEN IN THE TREATMENT OF ELDERLY PATIENTS WITH RELAPSED/REFRACTORY PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: Wenyu Shi
Journal: HemaSphere (2023)

Topic: 20. Lymphoma Biology & Translational Research Background: Primary central nervous system lymphoma (PCNSL) is an aggressive type of non-Hodgkin lymphoma that originates in the brain, spinal cord, eyes, or pia mater without systemic involvement. It accounts for about 3% of central nervous system tumors and has a poor prognosis, with most patients eventually relapsing and a 5-year survival rate of 29.6%. Zanubrutinib is a new generation BTK inhibitor that can penetrate the blood-brain barrier and is used in the treatment of PCNSL. Aims: This study aims to investigate the efficacy and safety of a zanubrutinib-based combination regimen in the treatment of elderly patients with relapsed/refractory (R/R) PCNSL. Methods: The study retrospectively analyzed elderly patients with R/R PCNSL who received a zanubrutinib-based combination regimen at the Affiliated Hospital of Nantong University in recent years. The study also collected information on patients diagnosed with PCNSL in the SEER project of the National Cancer Institute (NCI) and analyzed their survival status. In addition, the study used CCK8 and EdU to detect the effect of zanubrutinib on the viability and proliferation of activated B-cell subtype (ABC) diffuse large B-cell lymphoma (DLBCL) cell lines with genotypes similar to PCNSL. Results: The 7 elderly R/R PCNSL patients treated with the zanubrutinib-based regimen (zanubrutinib, rituximab, and temozolomide) showed an overall response rate (ORR) of 85.7% (6/7), a complete response (CR) of 57.1% (4/7), and a partial response (PR) of 28.6% (2/7), and 14.3% (1/7) of patients experienced disease progression (PD). The study found that patients’ gender, KPS score, ECOG score, surgical treatment or not, and positive cerebrospinal fluid protein were not significantly associated with the treatment effect. However, pathological type and IESLG score were related to treatment effect (P<0.05). The median progression-free survival (PFS) and median overall survival (OS) of patients in this study were not reached. The study analyzed clinical data of PCNSL patients in the SEER database from 1975 to 2016 and found that elderly patients (age>60 years old) and male PCNSL patients had a worse prognosis, and the primary site of PCNSL, treatment methods, and disease choice had an impact on the prognosis. There was no significant difference between the disease and other causes in terms of the cause of death. In the survival analysis of elderly patients, gender, surgery and radiotherapy sequence had no significant effect on prognosis, and patients who received chemotherapy had better OS than those who received radiotherapy. The study found that the cell viability of ABC subtype DLBCL cell line OCI-Ly10 decreased in a concentration- and time-dependent manner with zanubrutinib and temozolomide (P<0.05). The inhibitory effect of zanubrutinib and temozolomide on the proliferation of OCI-Ly10 cell line was stronger than that of single drug. Summary/Conclusion: The study showed that zanubrutinib-based combination therapy has good efficacy and controllable safety in elderly R/R PCNSL patients. The prognosis of elderly patients is poor, and the OS of chemotherapy patients is better than that of radiotherapy among the treatment options in the pre-BTKi era. Zanubrutinib can inhibit cell viability and cell proliferation in ABC subtype DLBCL cell line OCI-Ly10. Keywords: B cell lymphoma